Water → HCID 57066427, compound

HRID 1375012Notes

Reaction equation

HRID 1375012 reaction equation
[F:1][C:2]([F:50])([F:49])[C:3]1[CH:4]=[C:5]([CH:42]=[C:43]([C:45]([F:48])([F:47])[F:46])[CH:44]=1)[C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][N:16]2[CH2:21][CH2:20][O:19][C@H:18]([CH2:22][O:23][CH3:24])[CH2:17]2)[CH2:10][C@H:9]1[CH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH3:32])=[C:28]([NH:33][CH2:34][N:35]2[C:39](=[O:40])[CH2:38][CH2:37][C:36]2=[O:41])[CH:27]=1)=[O:7].[BH4-].[Na+].O.C(OCC)(=O)C>CS(C)=O>[F:48][C:45]([F:46])([F:47])[C:43]1[CH:42]=[C:5]([CH:4]=[C:3]([C:2]([F:1])([F:49])[F:50])[CH:44]=1)[C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][N:16]2[CH2:21][CH2:20][O:19][C@H:18]([CH2:22][O:23][CH3:24])[CH2:17]2)[CH2:10][C@H:9]1[CH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH3:32])=[C:28]([NH:33][CH3:34])[CH:27]=1)=[O:7].[F:47][C:45]([F:46])([F:48])[C:43]1[CH:42]=[C:5]([CH:4]=[C:3]([C:2]([F:50])([F:49])[F:1])[CH:44]=1)[C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][N:16]2[CH2:21][CH2:20][O:19][C@H:18]([CH2:22][O:23][CH3:24])[CH2:17]2)[CH2:10][C@H:9]1[CH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH3:32])=[C:28]([NH:33][CH2:34][N:35]2[CH:39]([OH:40])[CH2:38][CH2:37][C:36]2=[O:41])[CH:27]=1)=[O:7]

Participants

7

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 4311764Sodium borohydrideHCID 86602701HCID 86602701, compound

Product 2

HCID 57066427HCID 57066427, compoundHCID 57070026HCID 57070026, compound

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
80 °C

Procedure

A solution of (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-[4-methyl-3-[[(2,5-dioxopyrrolidino)methyl]amino]benzyl]-4-[2-[(2S)-2-(methoxymethyl)morpholino]ethyl]piperazine (0.14 g) in dimethylsulfoxide (0.42 ml) was added sodium borohydride (10 mg) and the whole was stirred at 80° C. for 15 hours. After cooling, water and ethyl acetate were added to the mixture. The organic layer was separated, washed with brine, dried over sodium sulfate and evaporated in vacuo. The residue was purified by column chromatography on silica gel with a mixture of methylene chloride and methanol (30:1 to 10:1) as eluent to give (2R)-1-[3,5-bis(trifluoromethyl)-benzoyl]-2-[4-methyl-3-(methylamino)benzyl]-4-[2-[(2S)-2-(methoxymethyl)morpholino]ethyl]piperazine (37 mg) and (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-[4-methyl-3-[[(5-hydroxy-2-oxopyrrolidino)methyl]amino]benzyl]-4-[2-[(2S)-2-(methoxymethyl)morpholino]ethyl]piperazine (45 mg), respectively. Each compound was converted to its trihydrochloride in a conventional manner.

Workup

  1. temperatureAfter cooling
  2. customThe organic layer was separated
  3. washwashed with brine
  4. dry with materialdried over sodium sulfate
  5. customevaporated in vacuo
  6. customThe residue was purified by column chromatography on silica gel with a mixture of methylene chloride and methanol (30:1 to 10:1) as eluent

Sources & evidence

ORD record
ord-9ae7b0bcf51e4c479881a67f329cdafa
Source dataset
uspto-grants-2007_01
Patent number
US07166598B2

Reaction notes

Loading…